Comprehensive gene expression profiling identifies distinct and overlapping transcriptional profiles in non-specific interstitial pneumonia and idiopathic pulmonary fibrosis

• Published in: Respiratory research Vol. 19; no. 1; p. 153
• Main Authors: Cecchini, Matthew J, Hosein, Karishma, Howlett, Christopher J, Joseph, Mariamma, Mura, Marco
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 15.08.2018; BioMed Central; BMC
• Subjects: Adult; Aged; Biopsy; Cell cycle; Cluster analysis; Clustering; Collagen; Control; Control methods; DNA microarrays; Female; Fibroblasts; Fibrosis; Gene expression; Gene Expression Profiling - methods; Genes; Genetic aspects; Humans; Hypotheses; Idiopathic Interstitial Pneumonias - diagnostic imaging; Idiopathic Interstitial Pneumonias - genetics; Idiopathic pulmonary fibrosis; Idiopathic Pulmonary Fibrosis - diagnostic imaging; Idiopathic Pulmonary Fibrosis - genetics; Immunohistochemistry; Leukocyte migration; Leukocytes; Lung - pathology; Lung diseases; Lungs; Lymphocytes T; Male; Mesenchyme; Microarray; Middle Aged; Non-specific interstitial pneumonia; Patients; Pneumonia; Proteins; Pulmonary fibrosis; Risk analysis; Risk factors; Senescence; Serology; Serum levels; Subgroups; Transcription; Transcription (Genetics); Transcription, Genetic - genetics; Usual interstitial pneumonia; Non-specific interstitial pneumonia; Usual interstitial pneumonia; Microarray; Idiopathic pulmonary fibrosis
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/s12931-018-0857-1

The clinical-radiographic distinction between idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP) is challenging. We sought to investigate the gene expression profiles of IPF and NSIP vs. normal controls. Gene expression from explanted lungs of patients with IPF (n = 22), NSIP (n = 10) and from normal controls (n = 11) was assessed. Microarray analysis included Significance Analysis of Microarray (SAM), Ingenuity Pathway, Gene-Set Enrichment and unsupervised hierarchical clustering analyses. Immunohistochemistry and serology of proteins of interest were conducted. NSIP cases were significantly enriched for genes related to mechanisms of immune reaction, such as T-cell response and recruitment of leukocytes into the lung compartment. In IPF, in contrast, these involved senescence, epithelial-to-mesenchymal transition, myofibroblast differentiation and collagen deposition. Unlike the IPF group, NSIP cases exhibited a strikingly homogenous gene signature. Clustering analysis identified a subgroup of IPF patients with intermediate and ambiguous expression of SAM-selected genes, with the interesting upregulation of both NSIP-specific and senescence-related genes. Immunohistochemistry for p16, a senescence marker, on fibroblasts differentiated most IPF cases from NSIP. Serial serum levels of periostin, a senescence effector, predicted clinical progression in a cohort of patients with IPF. Comprehensive gene expression profiling in explanted lungs identifies distinct transcriptional profiles and differentially expressed genes in IPF and NSIP, supporting the notion of NSIP as a standalone condition. Potential gene and protein markers to discriminate IPF from NSIP were identified, with a prominent role of senescence in IPF. The finding of a subgroup of IPF patients with transcriptional features of both NSIP and senescence raises the hypothesis that "senescent" NSIP may represent a risk factor to develop superimposed IPF.